Explore the origin of the flexibility of blood clots

How do blood clots maintain the correct balance of stiffness to heal wounds and flexibility to move in the blood stream?

Scientists at the University of Pennsylvania School of Medicine and the Faculty of Arts - Science have demonstrated that there is a protein structure capable of acting as a molecular spring, partly to help explain that the clots Blood can stretch and bend under the pressure that occurs in the body like the flow of blood. The scientists published their findings in ' Letter ' in the latest online edition of the Biophysical Journal. This understanding will help scientists know the physiology of blood clots in conditions such as wound healing, stroke and cardiovascular diseases.

The Fibrinogen molecule pulled by the probe of an atomic force microscope (yellow disc) expands 23 nanometers thanks to the straightening of three tightly wound loops in the molecule.(Photo by John Weisel, Ph.D., University of Pennsylvania School of Medicine; Biophysical Journal)

Blood clots are a network of three-dimensional blood fibers

Thanh Van

, which is made up primarily of blood proteins, fibrinogen, a plasma substance (coagulation factor) and changes into fibrin in the process of clotting. A blood clot needs to have the right stiffness and ductility to hold the flow of blood when the tissue is damaged but it should be soft enough so that it does not prevent blood flow and cause heart attacks and strokes.

In the previous study, Dr. John W. Weisel, professor of cell and developmental biology, measured the elasticity of individual blood fibers and found that the blood fibers, the fibers are long and very thin, bent much easier than when stretched, which indicates that deformed clots in blood flow are flowing or under other pressures, mainly due to the bending of their blood fibers

The present study extends previous discoveries at the molecular level, demonstrating that individual blood fibers bend due to the partial separation of tightly coiled rod-like regions in the feces. Fibrinogen, called a wire loop, is wound in an alpha helix. Using atomic force microscopy, the scientists measured this change by pulling the fibrinogen molecular strands that had been changed to the genetic structure. This alpha spiral-shaped 'spring' is a familiar model in protein structure, first identified 50 years ago and so its stretchability may have greater significance in biology. and medicine.

By understanding the mechanical process at the molecular level, understanding how this process is related to the mechanical properties of individual blood fibers and the whole clot may be done. OK. This understanding could help scientists predict the function of fibrin clots (these clots are formed differently) in blood flow or in a wound. For example, if clots are not strong enough, problems with bleeding will arise, and if clots are too hard, problems with congestion can occur, when the disease occurs. Clots that block blood flow. The first author André Brown, a bachelor in physics at Penn University, noted that this study is the first step in understanding the mechanical properties of the relationship between the elasticity of blood clots and diseases.

A recent study by other scientists has now demonstrated that fibrin fibers can stretch 4 to 5 times their original length before being broken. 'This is one of the most elastic polymers anyone knows,' said Weisel. 'But, how does this relaxation occur at the molecular level? We think that part of the elasticity is necessarily the opening of certain parts of the fibrin molecule, otherwise how can it stretch so much? '

Previous research from Dr. Dennis Discher demonstrated that the alpha helix structure in some of the blood cells' proteins could open at low mechanical forces. But 'previously it was not known that the alpha-spiral wrap of the fibrinogen molecule would be a part of the pressure created by the atomic force microscope,' Brown notes.

Once the origin of the mechanical properties of clots is well understood, the adjustment of these properties may be possible, the authors of this study noted. 'If we can change a certain parameter, then perhaps we are able to make a clot become harder or softer.' Professor Weisel explained. For example, different peptides or proteins, such as antibodies, are always linked to fibrin, affecting the structure of blood clots. The idea is to use such compounds in humans to change the properties of blood clots, so it can become less dangerous or easier to dissolve.

In the future, scientists will examine other processes at the molecular level and at the level of blood fiber, levels may be responsible for the mechanical properties of blood clots, thereby developing tissue. The image can be used to predict the effect of regional changes on coagulation properties in other regions. One such picture will be helpful in developing treatments for disease and disease prevention for a variety of cardiovascular and stroke conditions.